Search Results (449)

Human papillomavirus (HPV) is one of the most widespread sexually transmitted infections globally, whose persistent infection plays a major role in causing cervical cancer. Vaccination is therefore a key prevention strategy. Using a gender-stratified dynamic transmission model tailored to a Tunisian case, we investigate the impact of bivalent HPV vaccination. The proposed model accounts for partial cross-immunity and captures both direct and indirect effects of female-only vaccination. We derive the basic reproduction number and the corresponding herd immunity threshold, and a global sensitivity analysis shows that vaccine coverage, efficacy, and cross-protection are strong drivers of transmission reduction. Their combined effects on disease spread are quantified by varying these parameters across biologically relevant ranges. An optimal control problem was formulated and analyzed using Pontryagin’s Maximum Principle to minimize persistent infections and cancer cases while limiting vaccination effort. Three vaccination scenarios are compared: an ideal case with full vaccine availability and two resource-constrained cases with respective maximum coverage rates of $100\%$ and $80\%$. The numerical simulations revealed that the optimal strategy under unconstrained conditions can achieve significant suppression of infection, persistence, and cancer. Under constrained effort, the optimal control still achieves substantial reductions in disease burden, with minor differences in dynamics and speed of immunity buildup. Our results highlight the effectiveness of female-only HPV vaccination in providing both direct and indirect protection. They also emphasize the importance of sustained coverage in constrained settings. Full article

Pear fire blight, caused by the bacterium Erwinia amylovora, is a destructive disease affecting Rosaceae plants. Although insect transmission is well-documented, most studies have focused on pollinators, with limited attention to psyllids. Chinese pear psyllid (Cacopsylla chinensis) is a major piercing–sucking pest of pear trees, yet its role in the transmission of E. amylovora remains unclear. Here, we investigated the distribution of E. amylovora in and on C. chinensis and the synergistic damage (i.e., C. chinensis creates invasion wounds and nutrient-rich niches for E. amylovora via piercing–sucking feeding, while the pathogen enhances the vector’s fitness to promote disease spread). Field and laboratory assays confirmed severe synergistic symptoms. E. amylovora was isolated from all life stages and body parts of C. chinensis, with significantly higher pathogen loads and virulence in internally harbored strains compared to external ones. Specifically, E. amylovora loads in nymphs were significantly higher than those in adults, and strains from the digestive system and female reproductive organs caused a 3- to 9-fold higher disease index on pear leaves at 7 days post-inoculation compared to body surface isolates. This study provides evidence that C. chinensis acts as a crucial vector for E. amylovora in Xinjiang, laying a theoretical basis for the precise integrated management of this pest–disease complex. Full article

Background/Objectives: Intermittent fasting (IF) has gained increasing attention as a nutritional strategy to improve metabolic health, body composition, and disease-related outcomes. However, its effects are often interpreted as broadly uniform, despite growing evidence that biological sex may modulate fasting responses. This narrative review examines sex-specific differences in the physiological, endocrine, clinical, and psychosocial effects of IF in women and men. Methods: We conducted a narrative synthesis of human and preclinical evidence addressing IF protocols, mechanisms, benefits, adverse effects, and sex-related differences. Particular attention was given to substrate metabolism, hormonal regulation, neuroendocrine sensitivity, energy availability, exercise performance, chronic disease management, aging-related outcomes, and psychological or behavioral responses. Results: The available literature suggests that women and men share several beneficial responses to IF, including improvements in body composition and cardiometabolic markers, but may differ in the magnitude, tolerability, and mechanistic basis of these effects. Women appear to show greater sensitivity of reproductive and neuroendocrine function to energetic stress, particularly under conditions of low energy availability, high exercise load, or reproductive vulnerability. In contrast, men may exhibit preserved functional outcomes despite measurable endocrine adaptations, including changes in testosterone dynamics. Across both sexes, responses vary according to fasting protocol, nutritional adequacy, baseline metabolic status, life stage, and clinical context. Conclusions: Current evidence supports a sex-informed and context-specific interpretation of IF rather than universally applicable fasting prescriptions. Direct sex-comparative studies remain scarce, and many conclusions are inferred from parallel male and female studies. Future research should integrate sex as a core biological variable in precision nutrition and fasting-based interventions. Full article

Chemical modifications of RNA add a dynamic regulatory layer to gene expression beyond the genome and epigenome. Among these modifications, 5-methylcytidine (m⁵C) has emerged as a key epitranscriptomic modification that influences RNA stability, translation, localization, and stress responses across diverse biological systems. Recent advances in high-resolution mapping and functional interrogation of m⁵C have revealed its involvement in development, metabolism, immune regulation, and disease pathogenesis. Notably, many of these processes are highly relevant to women’s health, which is shaped by hormone-responsive tissues, reproductive transitions, and pregnancy-associated physiological adaptations. In this review, we provide a comprehensive and integrative overview of m⁵C RNA modification with a focus on its roles in female biology and disease. We summarize the molecular machinery responsible for m⁵C deposition, recognition, and regulation, as well as current detection technologies. We further highlight emerging evidence linking m⁵C dysregulation to early embryonic development, women-specific cancers, gynecologic and reproductive disorders, pregnancy complications, and metabolic and cardiovascular diseases. In addition, we discuss the interplay between m⁵C and sex hormone signaling, as well as the potential of m⁵C as a biomarker and therapeutic target. Finally, we identify key knowledge gaps, including the need for tissue-specific, longitudinal, single-cell, and spatial epitranscriptomic studies in women. By integrating epitranscriptomics into women’s health research, this review underscores m⁵C as a previously underappreciated regulatory layer with significant implications for precision medicine and clinical translation. Full article

The global rise in obesity and cardiometabolic disease represents a major public health concern and contributes significantly to cardiovascular morbidity and mortality. Contemporary Western dietary patterns and excess adiposity are strongly associated with atherosclerotic cardiovascular disease. Although pharmacologic therapies have expanded, lifestyle interventions remain the cornerstone of prevention and management. However, identifying sustainable and effective dietary approaches continues to be challenging given the wide range of available nutrition regimens. Intermittent fasting (IF) has emerged as a promising strategy for weight reduction and metabolic improvement. In this article, we review the physiological effects of IF, including metabolic switching, ketosis, and improvements in insulin sensitivity and inflammatory regulation. We also evaluate clinical evidence regarding the impact on cardiovascular risk, as well as its safety and tolerability. We examine the hormonal responses to IF based on sex. While early studies raised concerns regarding potential reproductive and endocrine disturbances, recent data suggest beneficial effects in both males and females. IF may modestly reduce testosterone in men without impairing muscle mass or strength and may improve metabolic and reproductive outcomes in women, particularly those with hyperandrogenic conditions such as polycystic ovarian syndrome, with favorable effects also observed in postmenopausal women, especially when combined with physical activity. Full article

Gonadectomy is performed in bitches to prevent unwanted reproduction and reduce the risk of sex hormone-related conditions. However, growing evidence suggests that the timing of spaying may influence long-term susceptibility to non-reproductive diseases. This retrospective case–control study (2013–2023) evaluated the association between timing of spaying and the development of orthopedic and neoplastic disorders in a Belgian referral-hospital population. Cases included bitches diagnosed with cranial cruciate ligament rupture, hip dysplasia, elbow dysplasia, lymphoma, mast cell tumor, osteosarcoma, or hemangiosarcoma, while disease-free bitches served as controls. Associations between disease occurrence and spaying status were assessed using multivariable logistic regression adjusted for age, weight category, and body condition score. Age at gonadectomy (<12 vs. ≥12 months) and timing relative to the first estrus were evaluated in separate models. Spaying <12 months of age was associated with increased odds of all conditions compared with intact females. Spaying ≥12 months of age was associated with lower odds of several orthopedic and neoplastic outcomes compared with early spaying, although odds were not always comparable to those in intact females. Large body size and higher body condition score were independently associated with increased odds of orthopedic outcomes. These findings support individualized spaying strategies rather than a universal age threshold. Full article

Conventional hormonal and clinical models inadequately clarify the complex and diverse aspects of female infertility, resulting in poor reproductive outcomes and reduced egg viability. A growing body of research indicates that female reproductive failure is mostly due to disruptions in cellular homeostasis, especially concerning organelle quality control. Oxidative stress has emerged as a crucial mediator connecting metabolic, inflammatory, and ageing-related processes to ovarian failure, however its downstream impacts on intracellular organelle turnover remain insufficiently clarified. Our narrative review encapsulates the existing data for a unified pathogenic concept focused on the redox-regulated mitochondria–lysosome axis. We examine the interaction of oxidative stress, mitochondrial malfunction, compromised mitophagy, and lysosomal deficiency in granulosa cells and oocytes. Prolonged oxidative stress may disrupt this equilibrium, leading to defective mitochondria accumulation and impaired mitophagy. This self-perpetuating cycle may ultimately jeopardises reproductive viability and oocyte integrity. The integrated axis offers a shared molecular foundation for various infertility-related diseases, such as inadequate ovarian response, obesity-associated infertility, polycystic ovary syndrome, and ovarian ageing. Ultimately, we analyse new findings suggesting that specific antioxidant chemicals modify mitophagy and lysosomal function while also neutralising reactive oxygen species, highlighting their potential use in precision fertility treatments. Our research redefines female infertility as a condition of redox-dependent organelle quality control, thereby introducing novel avenues for identifying biomarkers, categorising patients, and targeting treatments in assisted reproduction. Full article

Background/Objective: RNA modifications, including N⁶-methyladenosine (m⁶A), 5-methylcytosine (m⁵C), 7-methylguanosine (m⁷G), N¹-methyladenosine (m¹A), pseudouridine (Ψ), N⁴-acetylcytidine (ac⁴C), 5-methoxycarbonylmethyl-2-thiouridine (mcm⁵s²U) and adenosine-to-inosine (A-to-I) editing, constitute a critical layer of post-transcriptional regulation that influences RNA stability, splicing, translation and degradation. This review aims to systematically summarise the current understanding of the molecular mechanisms and regulatory networks of RNA modifications in the female reproductive physiology and to evaluate their pathological implications in obstetric and gynaecologic disorders. Methods: We conducted a comprehensive literature review, synthesising findings from high-throughput sequencing studies, functional experiments and clinical investigations. The review integrates evidence across multiple RNA modification types, their regulatory enzymes (writers, erasers and readers) and their roles in physiological processes (germ cell development, oocyte maturation, embryogenesis and endometrial function) and pathological conditions (gynaecologic cancers, preeclampsia, endometriosis, polycystic ovary syndrome and premature ovarian insufficiency). Results: RNA modifications function as dynamic and reversible regulators that orchestrate key reproductive events, including primordial germ cell differentiation, oocyte meiosis, the maternal-to-zygotic transition, the establishment of uterine receptivity, and placental development. These modifications operate through coordinated writer–eraser–reader networks that fine tune transcripts’ stability, translation efficiency and RNA decay. The dysregulation of these epitranscriptomic networks is strongly implicated in the pathogenesis of gynaecologic malignancies (cervical, ovarian, endometrial cancers and choriocarcinoma), pregnancy-related disorders (preeclampsia, gestational diabetes mellitus and recurrent miscarriage), reproductive endocrine disorders (polycystic ovary syndrome and premature ovarian insufficiency) and benign gynaecological conditions (endometriosis and adenomyosis). Emerging evidence also reveals complex crosstalk among RNA modifications, such as cooperative interactions between m⁶A and m⁵C in translation regulation and antagonistic relationships between m⁶A and A-to-I editing. Conclusions: RNA modifications represent an essential and multifaceted regulatory layer in female reproduction, with broad implications for disease pathogenesis. Their unique reversibility and context-dependent functions offer promising opportunities for the development of diagnostic biomarkers and targeted therapeutic interventions. Future researchers should prioritise integrated multi-omics approaches, enhanced human-relevant models and clinical translation to fully realise the potential of epitranscriptomic medicine in reproductive health. Full article

Gonadotropin-releasing hormone 1 (GnRH1) and its receptor (GnRHR1) are central neuropeptides on the hypothalamic–hypophysis–gonadal (HHG) axis and play key roles in vertebrate reproduction. Although GnRH1/GnRHR1 signaling has been extensively studied in models such as mouse, rat, zebrafish, and human, knowledge from other species is limited. This work used cloning, Sanger sequencing, and qPCR to highlight the molecular structure, evolutionary history, and sex-differentiated transcription of GnRH1/GnRHR1 signaling from hamster. These findings showed that GnRH1/GnRHR1 hamster proteins exhibit a molecular evolutionary history highly similar for peptides reported in other species and with which they share a high degree of structural homology. Expression profiles indicated a GnRH1 transcript in several tissues with higher expression levels in testes, adrenals, uterus, epididymis, female hypothalamus, and Harderian glands. GnRHR1 expression levels were seen exclusively in male and female hypophysis with higher levels in female hypophysis. Expression levels showed significant differences for GnRH1 in several tissues during estrous; GnRHR1 expression during estrous was detected only in hypophysis with increased expression levels seen during metestrus and diestrus. These results suggest a highly conserved homology of GnRHR1/GnRHR1 signaling, thus highlighting its evolutionary importance. These expression levels underscore the importance of GnRHR1 as a master regulator of reproductive endocrinology and could implicate hamster peptides as potential therapeutic biological models for human endocrine diseases. Full article

The immune system is a pivotal regulator of reproductive physiology, maintaining tissue homeostasis essential for successful pregnancy while contributing to infertility and reproductive disorders when dysregulated. Natural products represent a valuable source of novel immunomodulatory agents. Icariin (ICA), a prenylated flavonoid glycoside isolated from Epimedium species (Horny Goat Weed), has a long-standing traditional use for “invigorating yang,” which modern research attributes to its reproductive function-enhancing properties. This review synthesizes emerging evidence that the beneficial effects of ICA on female and male reproductive health are primarily mediated through its sophisticated immunomodulatory actions on the reproductive–immune axis. We systematically dissect the molecular mechanisms by which ICA reprograms the reproductive immune microenvironment, focusing on its regulation of macrophage polarization, T-helper cell (Th1/Th2/Th17) and regulatory T-cell (Treg) balance, and suppression of key pro-inflammatory signaling pathways (NF-κB, NLRP3 inflammasome, JAK-STAT) in ovarian, uterine, and testicular tissues. This review provides a detailed account of how ICA modulates reproductive disorders via regulating immune responses, with the aim of offering innovative strategies for the design of novel immunomodulatory therapies targeting reproductive diseases. Full article

Background/Objectives: Endometrial cancer is one of the most common malignancies of the female reproductive system. Fortunately, risk-adapted therapy offers a promising chance of recovery, even from locally advanced disease. In particular, older patients with higher risk factors benefit markedly from adjuvant radiotherapy with or without chemotherapy. Nevertheless, this also carries a risk of higher cumulative toxicity thereafter. Although this phenomenon has been observed in older patients, it has not yet been adequately evaluated. Methods: This retrospective study compared the clinical features of patients receiving adjuvant radiotherapy with or without sequential chemotherapy or radiotherapy with concomitant chemotherapy between 2011 and 2023. The cohort was divided into two groups: patients over 65 years old and those under 65. Results: 100 patients received adjuvant radiotherapy at our center between 2011 and 2023. The mean age of patients was 66.87 years. We observed that neither diabetes, obesity, concurrent, sequential chemotherapy, nor para-aortic field irradiation was associated with an increased incidence of acute radiogenic side effects such as cystitis, diarrhea, proctitis, radiodermatitis, nausea, or vaginal dryness according to CTCAE ≥ 2 (all p > 0.50). No difference was found between the two groups in terms of the incidence of radiotherapy-associated toxicity. Conclusions: We found no increase in toxicity in elderly patients after adjuvant radiotherapy with or without chemotherapy. Full article

Background/Objectives: Acromegaly is a systemic connective tissue disease driven by chronic growth hormone (GH) and insulin-like growth factor-1 (IGF-1) excess; yet, the female reproductive tract—especially the extracellular matrix (ECM)-rich cervix—has been poorly studied. We aimed to compare uterine and cervical morphology in women with acromegaly versus healthy controls and a gynecologic disease comparator, testing the hypothesis of selective cervical hypertrophy. Methods: We performed a retrospective case–control study of reproductive-age women who underwent pelvic ultrasound: acromegaly (n = 33), healthy controls (n = 45), and adenomyosis without acromegaly (n = 44). Uterine body measurements were obtained by TAUS/TVUS; cervical biometry was performed transvaginally in all cases. Volumes were estimated using the ellipsoid formula, and a uterus-to-cervix (U:C) volume ratio was calculated. Group differences were analyzed with Mann–Whitney tests and Bonferroni correction. Results: A total of 122 women were included. Uterine body length, width, AP size, and volume did not differ between acromegaly and either comparison group (all p-values non-significant). In contrast, cervical length, width, AP thickness, and volume were significantly higher in acromegaly than in healthy controls, with a corresponding reduction in the U:C volume ratio, indicating disproportionate cervical enlargement. Compared with adenomyosis, women with acromegaly again showed larger cervical width, AP thickness, and volume, together with altered U:C indices, whereas cervical length did not differ, suggesting a pattern not explained by nonspecific pelvic pathology. Conclusions: Women with acromegaly demonstrate a distinct uterine phenotype characterized by selective cervical hypertrophy with preserved uterine corpus size—an ECM-centric “acromegalic uteropathy.” This noninvasive morphometric signature may have diagnostic and procedural relevance and warrants confirmation in prospective studies. Full article

Background: Endometriosis is a major cause of female infertility. It significantly impacts oocyte quality and embryonic development. The condition’s pathophysiological mechanisms are multifactorial. However, they are believed to be reflected in the biochemical composition of follicular fluid (FF). FF is the immediate microenvironment of the developing oocyte hence its relevance. Conventional analytical methods provide only a limited view of this complex biofluid. This underlies the need for holistic profiling techniques. Objective: This narrative review synthesizes current knowledge on the potential of Fourier-Transform Infrared (FTIR) and Raman spectroscopy. The two are scrutinized as label-free, non-destructive tools for analyzing FF in the context of endometriosis. As such, the aim is to bridge the understanding of the disease’s impact on the follicular niche with the analytical power of these spectroscopic techniques, ultimately highlighting a critical research gap, while critically evaluating the translational pathway required to bring these techniques from research laboratories into routine clinical IVF practice. This includes assessment of practical feasibility, cost-effectiveness, turnaround time, standardization requirements, and comparison with existing clinical biomarkers. Methods: We outline the fundamental principles of FTIR and Raman spectroscopy and their complementary strengths. The review then consolidates evidence from proteomic and metabolomic studies demonstrating FF alterations in endometriosis. We also showcase the successful application of vibrational spectroscopy in other reproductive diagnostics. This synthesis is vital to identifying a specific unmet need in the field. Conclusions: Despite the known importance of FF and the proven capability of FTIR and Raman spectroscopy in related areas, there is a striking lack of studies applying these techniques directly to the FF of women with endometriosis. This review concludes by framing this void as a pivotal research opportunity. In doing so, it presents a direct rationale and methodological framework for a future study designed to characterize the unique spectral fingerprints of endometriosis in FF, with the goal of uncovering novel biomarkers and pathophysiological insights. Full article

The human microbiome has emerged as a central regulator of health and disease; however, women-specific microbiome research has only recently gained focused scientific attention. Accumulating evidence demonstrates that microbial ecosystems across the gut, vagina, skin, breast tissue, and reproductive tract are dynamically shaped by female hormones, life-stage transitions, and environmental exposures. These interactions influence immune regulation, metabolic homeostasis, reproductive outcomes, mental health, and cancer risk, in part through microbiome-mediated endocrine pathways such as the estrobolome. Advances in high-resolution molecular technologies—including metagenomics, metabolomics, spatial and single-cell profiling, and artificial intelligence-driven modeling—have shifted microbiome research from descriptive taxonomy toward functional, mechanistic, and predictive science. These approaches highlight microbial function and metabolite production as stronger determinants of health outcomes than taxonomic composition alone. Nonetheless, major gaps persist, including limited causal evidence, methodological heterogeneity, underrepresentation of non-Western populations, and barriers to clinical translation. Microbiome-targeted interventions, including probiotics, prebiotics, postbiotics, and emerging microbiota-based therapies, have garnered increasing interest in women’s health. Select Lactobacillus and Bifidobacterium strains show potential in modulating vaginal and gastrointestinal health, pregnancy outcomes, and immune function; however, clinical effects remain highly strain-specific and context-dependent. Discrepancies between experimental findings, commercial claims, and validated clinical use underscore the need for rigorous, women-centered trials and standardized outcome measures. This narrative review synthesizes current molecular insights into the women’s microbiome across endocrine interactions, pregnancy, reproductive and metabolic health, lifestyle influences, and microbiome-based therapeutic strategies. We integrate clinical perspectives to identify diagnostic and translational challenges and propose future directions emphasizing precision microbiome medicine, validated biomarkers, careful evaluation of microbiome-targeted interventions, and inclusive research frameworks, including populations from the Gulf Cooperation Council (GCC). Collectively, this review positions the microbiome as a critical yet underutilized axis in women’s health and outlines a roadmap toward personalized, evidence-based care across the female lifespan. Full article

Background/Objectives: Migraine is a leading cause of disability in women and is intricately linked to hormonal fluctuations and systemic health. This review aims to unravel the complex relationship between migraine, cardiovascular disease, and metabolic syndrome throughout the female reproductive lifespan. Methods: A comprehensive narrative review was conducted using the PubMed database for studies published between January 1988 and December 2025. Keywords included “migraine”, “cardiovascular risk”, “metabolic syndrome”, “pregnancy”, and “hormonal therapy”. Articles were selected to synthesize the latest pathophysiological evidence and clinical guidelines. Results: Migraine prevalence in women is two to threefold higher than in men, peaking during fertile age. Hormonal milestones, particularly estrogen withdrawal, trigger menstrual migraine. Metabolic syndrome is significantly more common in migraineurs than the general population. Obesity and insulin resistance have been associated with higher migraine attack frequency and severity. Experimental evidence suggests that hyperinsulinemia may sensitize TRPV1 receptors on trigeminal neurons and enhance CGRP release, potentially lowering the activation threshold for migraine attacks; however, direct confirmation of this pathway in humans remains limited. Furthermore, migraine with aura is linked to a doubled risk of ischemic stroke and increased risk of cardiovascular events. In pregnancy, migraine is an independent risk factor for stroke, myocardial infarction, and spontaneous coronary artery dissection. Conclusions: Migraine is a critical marker for cardiovascular and metabolic risk, necessitating routine screening and multidisciplinary management. Clinicians must prioritize cardiovascular counselling, metabolic evaluations, and careful monitoring in these patients, especially during pregnancy. Hormonal therapy choices should be individualized, preferring progestin-only contraceptives for those with aura and transdermal routes for hormone replacement therapy to minimize cardiometabolic impact. Full article